CD8+ T cells (TCD8+) recognize class I molecules of the major histocompatibility complex (MHC) bearing peptides of 8 to 10 residues derived from cytosolic proteins. These cells constitute an important weapon in host defenses to infectious agents and tumors, and it is critical to understand how antigenic peptides are generated by cells if we are to improve existing vaccines and develop new vaccines and treatments for infectious and neoplastic diseases. There are large gaps in our knowledge of how cells produce antigenic peptides from proteins. While it is clear that proteolytic production of peptides begins in the cytosol, it is uncertain to what extent trimming occurs after peptides are translocated into the endoplasmic reticulum (ER). In this project we are investigating the processing of peptides in the ER.